非房室分析随机安慰剂对照试验结果评估实验性疼痛模型。

Evaluation of an Experimental Pain Model by Noncompartmental Analysis of Results from a Randomized Placebo Controlled Trial.

机构信息

Department of Pain Management, Fujian Provincial Hospital, Fujian Key Laboratory of Geriatrics, Provincial Clinic College of Fujian Medical University, Fuzhou, Fujian, China.

Faculté de pharmacie, Université de Montréal, Québec, Canada; Certara Consulting Services, Montréal, Québec, Canada.

出版信息

Pain Physician. 2018 Jul;21(4):363-372.

PMID:30045593

Abstract

BACKGROUND

Understanding analgesic pharmacodynamics (PD) in the elderly is key to optimising pain management. Electrically stimulated pain models (ESPM) permit assessment of pain responses in humans. C and A-delta sensory fibres convey pain and respond to low frequency electrical stimulus (5 and 250 Hz, respectively). Human research suggests pain tolerance threshold (PTT) is similar or decreases with age.

OBJECTIVES

To determine whether an ESPM is able to detect a difference in PTT in elderly (>/= 75 years) and young (20-40 years) subjects after single dose administration of a placebo and tramadol, a low potency analgesic.

STUDY DESIGN

Two-cohort, randomized, placebo-controlled, cross-over study.

METHODS

A noncompartmental analysis of data at 17 timepoints on 5 Hz and 250 Hz PTT over 24 h.

RESULTS

Young (16) and elderly (13) patients showed similar baseline (E0) PTT between active and placebo both overall and by age group in both frequencies. Net drug effect took into account negative and positive changes from E0. In the elderly, net peak effect on PTT produced by active treatment was significantly greater for both 5 Hz (34%) and 250 Hz (30%). Net area under the 24-h effect-time curve during active treatment was significantly higher for both 5 Hz (163 %) and 250 Hz (175%) stimulations in the elderly. No clinically significant difference was observed in the young.

LIMITATIONS

High variability in young subjects, despite efforts to remove outliers limited our ability to draw conclusions in that age group. Generalizability of results obtained from an experimental pain model in volunteers to treatment of elderly patients may be limited.

CONCLUSION

ESPM can detect a difference for pain tolerance threshold between placebo and tramadol administration in the elderly. Although both 5 Hz and 250 Hz stimulations can detect a difference, the effect size for 5 Hz is larger and seems more precise and reliable, particularly in the elderly.

KEY WORDS

Electrical pain model, elderly, geriatric, tramadol, placebo, opioid, area under the effect curve, noncompartmental analysis.

摘要

背景

了解老年人的镇痛药效动力学（PD）是优化疼痛管理的关键。电刺激疼痛模型（ESPM）允许评估人类的疼痛反应。C 和 A-delta 感觉纤维传递疼痛，并分别对低频电刺激（5 和 250 Hz）作出反应。人类研究表明，疼痛耐受阈值（PTT）随年龄的增长而相似或降低。

目的

确定在单次给予安慰剂和曲马多（一种低效能镇痛药）后，ESPM 是否能够检测到老年（>= 75 岁）和年轻（20-40 岁）受试者的 PTT 差异。

研究设计

两队列、随机、安慰剂对照、交叉研究。

方法

在 24 小时内的 17 个时间点上，对 5 Hz 和 250 Hz PTT 的非房室数据分析。

结果

年轻（16 岁）和老年（13 岁）患者在两种频率下，无论在活性组还是安慰剂组，整体和按年龄组，E0 时的基础 PTT 均相似。药物净效应考虑了 E0 时的正负变化。在老年人中，活性治疗对 PTT 的净峰值效应在 5 Hz（34%）和 250 Hz（30%）均显著更大。在老年人中，在活性治疗期间，24 小时效应-时间曲线下的净面积在 5 Hz（163%）和 250 Hz（175%）刺激下均显著升高。在年轻人中未观察到有临床意义的差异。